Risks and benefits of systematic lymphadenectomy during interval debulking surgery for advanced high grade serous ovarian cancer

ObjectivesTo assess outcomes and patterns of recurrence in patients with high-grade serous ovarian/tubal/primary peritoneal cancers with radiographic supraclavicular lymphadenopathy at diagnosis.MethodsWe evaluated all patients with newly diagnosed high-grade serous ovarian cancers treated at our center between January 1, 2008 and May 1, 2013 who had supraclavicular lymphadenopathy (defined as ≥1 cm in short axis) on radiographic imaging (either computed tomography or positron emission tomography) at the time of diagnosis.ResultsOf 586 patients with high-grade serous ovarian cancer receiving primary treatment during the study period, we identified 13 (2.2%) with supraclavicular lymphadenopathy diagnosed on pre-treatment imaging. The median age at diagnosis was 52.0 years (range 38.2–72.3). Five (31%) had clinically palpable nodes on physical examination. Four (31%) had a known BRCA mutation. All 13 patients underwent neoadjuvant chemotherapy, followed by interval debulking surgery. Each patient received a median of four cycles of neoadjuvant intravenous chemotherapy (range 3–7). At interval debulking surgery, complete gross resection was achieved in nine (70%) patients, and optimal resection (0.1–1 cm residual disease) in four (30%). Eleven patients (85%) recurred; however, only one (8%) recurred in the supraclavicular lymph nodes. Median follow-up time was 44.3 months (range 22.4–95.0). Median progression-free survival for the cohort was 11.7 months (95% CI 9.2 to 14.1). Median overall survival was 44.3 months (95% CI 41.5 to 47.1). In patients obtaining complete gross resection at interval debulking surgery, median progression-free survival and overall survival were 13.9 months (95% CI 8.9 to 18.9) and 78.1 months (95% CI 11.1 to 145.1), respectively.ConclusionsIn our study, approximately 2% of patients with high-grade serous ovarian cancer presented with radiographic evidence of supraclavicular lymphadenopathy. Supraclavicular lymphadenopathy at diagnosis did not portend an unfavorable outcome when complete gross resection was achieved at interval debulking surgery.

Download Full-text

SOX2 is a promising predictor of relapse and death in advanced stage high-grade serous ovarian cancer patients with residual disease after debulking surgery

Molecular & Cellular Oncology ◽

10.1080/23723556.2020.1805094 ◽

2020 ◽

Vol 7 (6) ◽

pp. 1805094

Author(s):

Maria Bååth ◽

Sofia Westbom-Fremer ◽

Laura Martin de la Fuente ◽

Anna Ebbesson ◽

Juliette Davis ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Residual Disease ◽

High Grade ◽

Advanced Stage ◽

Serous Ovarian Cancer ◽

Debulking Surgery

Download Full-text

The detrimental effect of adopting interval debulking surgery in advanced stage low-grade serous ovarian cancer

Journal of Gynecologic Oncology ◽

10.3802/jgo.2019.30.e4 ◽

2019 ◽

Vol 30 (1) ◽

Cited By ~ 8

Author(s):

Giorgio Bogani ◽

Umberto Leone Roberti Maggiore ◽

Biagio Paolini ◽

Antonino Diito ◽

Fabio Martinelli ◽

...

Keyword(s):

Ovarian Cancer ◽

Detrimental Effect ◽

Low Grade ◽

Advanced Stage ◽

Serous Ovarian Cancer ◽

Debulking Surgery ◽

Interval Debulking Surgery

Download Full-text

Prolonged interruption of chemotherapy in patients undergoing delayed debulking surgery for advanced high grade serous ovarian cancer is associated with a worse prognosis

Gynecologic Oncology ◽

10.1016/j.ygyno.2020.04.048 ◽

2020 ◽

Vol 158 (1) ◽

pp. 54-58

Author(s):

Gemma Searle ◽

Rachel Pounds ◽

Andrew Phillips ◽

Sean Kehoe ◽

Janos Balega ◽

...

Keyword(s):

Ovarian Cancer ◽

High Grade ◽

Serous Ovarian Cancer ◽

Debulking Surgery ◽

Worse Prognosis

Download Full-text

Management of the Elderly Patients with High-Grade Serous Ovarian Cancer in the REAL-WORLD Setting

Current Oncology ◽

10.3390/curroncol28020110 ◽

2021 ◽

Vol 28 (2) ◽

pp. 1143-1152

Author(s):

Michalis Liontos ◽

Alkistis Papatheodoridi ◽

Angeliki Andrikopoulou ◽

Nikolaos Thomakos ◽

Dimitrios Haidopoulos ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Elderly Patients ◽

Cancer Patients ◽

Progression Free Survival ◽

Optimal Treatment ◽

High Grade ◽

Serous Ovarian Cancer ◽

Debulking Surgery ◽

Free Survival

Treatment of elderly patients with neoplasia is challenging. Age is a known prognostic factor in ovarian cancer but the optimal treatment of elderly patients has not been determined. We undertook a retrospective analysis to determine clinical practice in advanced-stage ovarian cancer patients older than 70 years of age. Methods: Medical records of women with high-grade serous ovarian cancer, stage III and IV were retrospectively analyzed. Results: A total of 735 patients were identified with a median age of 61.5 years. 22.4% among them were older than 70 years of age at diagnosis. First-line Progression-Free Survival (PFS) and Overall Survival (OS) were significantly worse in elderly patients in comparison to the younger ones [mPFS 11.3 months vs. 14.8 months, (p < 0.001) and mOS 30.2 months vs. 45.6 months (p < 0.001)]. However, elderly patients were characterized by worse ECOG-Performance Status and they were more frequently treated with Neoadjuvant Chemotherapy followed by Interval Debulking Surgery, while often they were more frequently denied debulking surgery compared to patients under 70 years of age. Moreover, elderly patients received more frequently monotherapy with platinum as frontline treatment. In contrast, there was no significant difference in the outcome of the debulking surgery in comparison to the younger patients or the frequency that gBRCA test was performed. Age over 70 years did not retain its significance for either Progression-Free Survival or Overall Survival when adjusted for all other reported prognostic factors. Conclusions: Elderly ovarian cancer patients have a worse prognosis. Comprehensive geriatric assessment should be performed for the optimal treatment of these patients.

Download Full-text

Pathologic distribution at the time of interval tumor reductive surgery informs personalized surgery for high-grade ovarian cancer

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2020-001597 ◽

2020 ◽

pp. ijgc-2020-001597

Author(s):

Courtney D Bailey ◽

Rebecca Previs ◽

Bryan M Fellman ◽

Tarrik Zaid ◽

Marilyn Huang ◽

...

Keyword(s):

Ovarian Cancer ◽

Neoadjuvant Chemotherapy ◽

Large Bowel ◽

Primary Tumor ◽

High Grade ◽

Debulking Surgery ◽

Primary Surgery ◽

Surgery Group ◽

Interval Debulking Surgery ◽

Interval Surgery

IntroductionThe surgical approach for interval debulking surgery after neoadjuvant chemotherapy has been extrapolated from primary tumor reductive surgery for high-grade ovarian cancer. The study objective was to compare pathologic distribution of malignancy at interval debulking surgery versus primary tumor reductive surgery.MethodsPatients with a diagnosis of high-grade serous or mixed, non-mucinous, epithelial ovarian, fallopian tube or primary peritoneal cancer who underwent neoadjuvant chemotherapy or primary tumor reductive surgery and had at least 6 months of follow-up were identified through tumor registry at a single institution from January 1995 to April 2016. Pathologic involvement of organs was categorized as macroscopic, microscopic, or no tumor. Statistical analyses included Mann-Whitney and Fisher’s exact tests.ResultsOf 918 patients identified, 366 (39.9%) patients underwent interval debulking surgery and 552 (60.1%) patients underwent primary tumor reductive surgery. Median age was 62.3 years (range 25.3–92.5). The majority of patients in the interval debulking surgery group were unstaged (261, 71.5%). In the patients who had a primary tumor reductive surgery, 406 (74.6%) had stage III disease. In both groups, the majority of patients had serous histology: 325 (90%) and 435 (78.8%) in the interval debulking and primary tumor reductive surgery groups, respectively. There was a statistically significant difference between disease distribution on the uterus between the groups; 31.4% of the patients undergoing interval debulking surgery had no evidence of uterine disease compared with 22.1% of primary tumor reductive surgery specimens (p<0.001). In the adnexa, there was macroscopic disease present in 253 (69.2%) and 482 (87.4%) of cases in the interval vs primary surgery groups, respectively (p<0.001). Within the omentum, no tumor was present in the omentum in 52 (14.2%) in the interval surgery group versus 91 (16.5%) in the primary surgery group (p<0.001). In the interval surgery group, there was no tumor involving the small and large bowel in 49 (13.4%) and 28 (7.7%) pathologic specimens, respectively. This was statistically significantly different from the small and large bowel in the primary surgery group, of which there was no tumor in 20 (3.6%, p<0.001) and 16 (2.9%, p<0.001) of cases, respectively.ConclusionIn patients undergoing interval debulking surgery, there was less macroscopic involvement of tumor in the uterus, adnexa and bowel compared with patients undergoing primary cytoreductive surgery.

Download Full-text

Cell-free tumor DNA in peri-operative blood samples from advanced high-grade serous ovarian cancer patients with and without complete resection.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.5555 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 5555-5555 ◽

Cited By ~ 1

Author(s):

Florian Heitz ◽

Sotirios Lakis ◽

Philipp Harter ◽

Jalid Sehouli ◽

Jatin Talwar ◽

...

Keyword(s):

Ovarian Cancer ◽

Residual Disease ◽

Complete Resection ◽

High Grade ◽

Serous Ovarian Cancer ◽

Debulking Surgery ◽

Tp53 Mutations ◽

Post Surgery ◽

Tumor Dna

5555 Background: Surgical outcome is an important prognostic factor in advanced high-grade serous ovarian cancer (HGOC). Intra-operative determination of residual disease may be prone to subjective bias. Methods: We prospectively collected and analyzed tumor tissue and plasma from 21 pts with FIGO IIIC-IV HGOC. All tumor specimen showed loss of TP53 in immunohistochemistry. Tumor DNA from tissue and peri-operative cell-free DNA at baseline (BL) and at d(ays) 1, d4 and d10 were subjected to comprehensive hybrid-capture based next-generation sequencing (NEO New Oncology GmbH, Cologne, Germany). Results: The initial cohort comprised 10 pts without (TR>0) and 11 pts with complete resection TR0, with a total of 43 somatic genomic alterations. TP53 was mutated in 20/21 (95.2%) of tissue samples and in 15/21 (71.4%) corresponding plasma samples at BL. Therefore, TP53 mutations were used as a molecular marker of circulating tumor DNA levels post-surgery. In the remaining 5 BL cases the TP53 mutations were either not present in plasma (N= 3) or rested below the detection limit (N= 2). In d1, d4 and d10 post-surgical samples, the sample specific TP53 mutations were detected in 12 out of 15, 10 out of 14 and in 7 out of 13 cases, respectively. TP53variant allele frequency (VAF) did not differ among TR0 and TR>0 at BL (mean= 1.91 versus 1.73, Mann-Whitney test p = 0.86) whereas it was significantly lower for TR0 at d1 (mean= 0.06 versus 2,06; p value= 0.002), d4 (mean= 0.07 versus 1.8; p= 0.04) and d10 (mean VAF= 0 versus 1.04; p= 0.008). Five out of 9 TR>0 cases showed at least one increase in VAF between d0 and any additional time-point. In 8 out of 9 mutations remained detectable at d10 (VAF: 0.076 – 3.26). By contrast, TR0 cases showed consistent reduction in VAF throughout the follow-up period which maximized at d10. Conclusions: Liquid biopsycan efficiently detect somatic mutations in the cfDNA of pts with HGOC following debulking surgery. Variation of the TP53 VAF in sequential post-surgical samples appears to be restricted to TR>0 cases, whereas in TR0 pts VAF progressively decreases. Liquid biopsy may hold promise as a tool for the objective determination of residual disease after debulking surgery.

Download Full-text

Therapeutic value of selective lymphadenectomy in interval debulking surgery for stage IIIc and IV epithelial ovarian cancer

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2018-000200 ◽

2019 ◽

Vol 29 (4) ◽

pp. 761-767 ◽

Cited By ~ 3

Author(s):

Nan Song ◽

Yunong Gao

Keyword(s):

Ovarian Cancer ◽

Neoadjuvant Chemotherapy ◽

Progression Free Survival ◽

Debulking Surgery ◽

Stage Iiic ◽

Free Survival ◽

Systematic Lymphadenectomy ◽

Interval Debulking Surgery ◽

Selective Lymphadenectomy ◽

Cox Analysis

ObjectiveThe role of selective lymphadenectomy at the time of interval debulking surgery in patients with advanced ovarian cancer remains a topic of debate. This study aimed to evaluate the value of selective lymphadenectomy during interval debulking surgery in patients with radiologic evidence of lymph node metastasis at initial diagnosis that ultimately become negative on imaging after neoadjuvant chemotherapy.MethodsA retrospective analysis including patients with stage IIIC–IV epithelial ovarian cancer and suspicious pelvic or para-aortic lymph node metastasis by imaging at diagnosis that resolved after neoadjuvant chemotherapy. The study was conducted from January 1996 to June 2016 with R0 interval debulking surgery. The patients with disease progression after neoadjuvant chemotherapy were excluded. Suspicious metastatic lymph nodes at initial diagnosis by computed tomography/magnetic resonance imaging were excised by selective lymphadenectomy. Survival curves were constructed by the Kaplan-Meier method, and a multivariate analysis was performed using Cox regression.ResultsThere were a total of 330 patients included in the analysis. Selective lymphadenectomy of suspicious nodes (Group 1) was performed in 145 patients. Systematic lymphadenectomy (Group 2) was performed in 118 patients. Sixty-seven patients did not undergo lymphadenectomy (Group 3). There were no significant differences in clinicopathologic features among the groups. Median progression-free survival was 28, 30.5, and 22 months in Groups 1, 2, and 3, respectively (log-rank, p=0.049). No-lymphadenectomy was an independent factor affecting progression-free survival (Cox analysis, HR=1.729, 95% CI 1.213 to 2.464, p=0.002), with no difference between Groups 1 and 2 (Cox analysis, HR=1.097, 95% CI 0.815 to 1.478, p=0.541). Median overall survival was 50, 59, and 57 months in Groups 1, 2, and 3, respectively (Cox analysis, p=0.566). Patients who underwent selective lymphadenectomy had lower 1-year frequencies of lower extremity lymphedema and lymphocysts than those with systematic lymphadenectomy (6.2% vs 33.1%, p<0.001, and 6.2 % vs 27.1%, p<0.001, respectively).ConclusionsExtent of lymphadenectomy (systematic or selective) had no significant impact on progression-free survival or overall survival. In addition, the risks of lower extremity lymphedema and lymphocysts were lower in patients who underwent selective lymphadenectomy.

Download Full-text